Bill D. Roebuck, PhD
Professor of Pharmacology & Toxicology
Pharmacology & Toxicology
Clemson University, BS 1968
Massachussetts Institute of Technology, MS 1971
Massachussetts Institute of Technology, PHD 1975
Program in Experimental and Molecular Medicine
Dept. of Pharmacology and Toxicology
Dartmouth Medical School
Hanover NH 03755
Office: Remsen 518
Asst. Phone: 603-650-1667
Modulation of toxic processes by dietary factors or nutritional status; evaluation of the effects of dietary dithiolethiones on prevention of liver cancer; chemoprevention of cancer.
Work in Dr. Roebuck's laboratory is in the area of chemical carcinogenesis and cancer chemoprevention. He conducts experiments in two different models of cancer, namely, the rat/aflatoxin model for liver cancer. The common theme of his studies is the modulation of cancer development by nutritional factors or chemicals that would or could be added to the diet of animals including humans. Experimental effects are quantified by mitotic activity, number and size of putative preneoplastic lesions, and incidence and multiplicity of cancers.
With respect to the study of liver carcinogenicity, experimental focus is on the inhibition of aflatoxin-induced hepatic cancer in rats and the mechanisms of carcinogenesis. Aflatoxin is the most potent of the naturally occurring carcinogens and is associated with liver cancer in many populations worldwide. It is widely believed that the total elimination of this carcinogen from the human environment is not possible. The prevention of liver cancer by the inclusion of various antioxidants and enzyme inducers into the diet is under investigation. In collaboration with Dr. Thomas J. Curphey at Dartmouth Medical School, we are chemically synthesizing and evaluating the structure-activity relationship of a class of chemoprotective chemicals, the dithiolethiones, in an effort to understand the molecular features that result in cancer chemoprotection against aflatoxin-induced liver cancer. This work involves extensive collaboration with Drs. T.W. Kensler and J.D. Groopman of Johns Hopkins University.
NIH/NCI CA39416 (Kensler, P.I.; subcontract from Johns Hopkins University) 02/01/99-01/31/04 Molecular Mechanisms of Chemoprevention: Dithiolethiones
Toxicology lectures; Medical Pharmacology Course
Global Environmental Health
Dr. Roebuck received his B.S. from Clemson University in South Carolina in 1968 and his M.S. and Ph.D. from the Massachusetts Institute of Technology in 1971 and 1975 respectively. He received further training as a postdoctoral fellow in the Department of Pharmacology, Case Western Reserve University Medical School and the Department of Pathology. In 1979 he joined the faculty at Dartmouth where he is currently a Professor in the Department of Pharmacology and Toxicology and Adjunct Professor of Environmental Studies at Dartmouth College. He is certificated in General Toxicology by the American Board of Toxicology.
Kensler TW, Curphey TJ, Maxiutenko Y, Roebuck BD. Chemoprotection by organosulfur inducers of phase 2 enzymes: Dithiolethiones and dithins. Drug Metabol Drug Interact. 2000;17(1-4):3-22. Review. (view details on MedLine)
Stoner G, Casto B, Ralston S, Roebuck B, Pereira C, Bailey G. Development of a multi-organ rat model for evaluating chemopreventive agents: Efficacy of indole-3-carbinol. Carcinogenesis. 2002 Feb;23(2):265-72. (view details on MedLine)
James PE, Madhani M, Roebuck BD, Jackson SK, Swartz HM. Endotoxin-induced liver hypoxia: defective oxygen delivery versus oxygen consumption. Nitric Oxide. 2002 Feb;6(1):18-28. (view details on MedLine)
Yates MS, Kwak MK, Egner PA, Groopman JD, Bodreddigari S, Sutter TR, Baumgartner KJ, Roebuck BD, Liby KT, Yore MM, Honda T, Gribble GW, Sporn MB, Kensler TW. Potent protection against aflatoxin-induced tumorigenesis through induction of Nrf2-regulated pathways by the triterpenoid 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole. Cancer Res. 2006 Feb 15;66(4):2488-94. (view details on MedLine)
Johnson DN, Egner PA, Obrian G, Glassbrook N, Roebuck BD, Sutter TR, Payne GA, Kensler TW, Groopman JD. Quantification of urinary aflatoxin B1 dialdehyde metabolites formed by aflatoxin aldehyde reductase using isotope dilution tandem mass spectrometry. Chem Res Toxicol. 2008 Mar;21(3):752-60. Epub 2008 Feb 12. (view details on MedLine)
Bodreddigari S, Jones LK, Egner PA, Groopman JD, Sutter CH, Roebuck BD, Guengerich FP, Kensler TW, Sutter TR. Protection against aflatoxin B1-induced cytotoxicity by expression of the cloned aflatoxin B1-aldehyde reductases rat AKR7A1 and human AKR7A3. Chem Res Toxicol. 2008 May;21(5):1134-42. Epub 2008 Apr 15. (view details on MedLine)